Skip to main content
SpringerLink
Log in

A peptide preparation protects cells in organotypic brain slices against cell death after glutamate intoxication

  • Published:
Journal of Neural Transmission Aims and scope Submit manuscript

Summary.

Cerebrolysin has been shown to have neurotrophic and neuroprotective potential similar to NGF or BDNF. In the present study organotypic brain slices were utilized to determine the neuroprotective effects of Cerebrolysin, in a glutamate lesion paradigm mimicking a key event in ischemia. The study focused on the effects of Cerebrolysin on both necrotic and apoptotic cell death. Two specific DNA intercalating dyes were used to distinguish the type of cell death. The drug effect was evaluated both microscopically and quantitatively before, 24 hours after and then again 8 days after the lesion. Cerebrolysin was added either before and after the lesion or after the lesion only. The most pronounced effect was seen with the drug added both prior to and after the glutamate lesioning. A treatment after the lesion only also counteracted necrosis and apoptosis. The results render the drug relevant for treating acute as well as chronic neurodegenerative diseases.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • DW Choi (1992) ArticleTitleExcitotoxic cell death. J Neurobiol 23 1261–1276 Occurrence Handle1361523 Occurrence Handle1:CAS:528:DyaK3sXhtl2qtL4%3D

    PubMed  CAS  Google Scholar 

  • JJ Cohen (1993) ArticleTitleApoptosis. Immunol Today 14 126–130 Occurrence Handle8466628 Occurrence Handle10.1016/0167-5699(93)90214-6 Occurrence Handle1:CAS:528:DyaK3sXitlWlu7w%3D

    Article  PubMed  CAS  Google Scholar 

  • A Fukuda K Muramatsu A Okabe Y Shimano H Hida I Fujimoto H Nishino (1998) ArticleTitleNMDA receptor-mediated differential laminar susceptibility to the intracellular Ca2+ accumulation induced by oxygen-glucose deprivation in rat neocortical slices. J Neurophysiol 79 430–438 Occurrence Handle9425211 Occurrence Handle1:CAS:528:DyaK1cXnsFajsA%3D%3D

    PubMed  CAS  Google Scholar 

  • AM Ghoumari C Ibanez M El Etr P Leclerc B Eychenne BW O‘Malley EE Baulieu M Schumacher (2003) ArticleTitleProgesterone and its metabolites increase myelin basic protein expression in organotypic slice cultures of rat cerebellum. J Neurochem 86 848–859 Occurrence Handle12887683 Occurrence Handle10.1046/j.1471-4159.2003.01881.x Occurrence Handle1:CAS:528:DC%2BD3sXmslOgs7c%3D

    Article  PubMed  CAS  Google Scholar 

  • B Hutter-Paier E Grygar M Fruhwirth I Temmel M Windisch (1998a) ArticleTitleFurther evidence that Cerebrolysin protects cortical neurons from neurodegeneration in vitro. J Neural Transm 53 IssueID[Suppl] 363–372 Occurrence Handle1:CAS:528:DyaK1cXmvVWntLs%3D

    CAS  Google Scholar 

  • B Hutter-Paier E Steiner M Windisch (1998b) ArticleTitleCerebrolysin protects isolated cortical neurons from neurodegeneration after brief histotoxic hypoxia. J Neural Transm 53 IssueID[Suppl] 351–361 Occurrence Handle1:CAS:528:DyaK1cXmvVWntLo%3D

    CAS  Google Scholar 

  • JF Kerr AH Wyllie AR Currie (1972) ArticleTitleApoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 26 239–257 Occurrence Handle4561027 Occurrence Handle1:STN:280:CSyD3crgslU%3D

    PubMed  CAS  Google Scholar 

  • RR Leker E Shohami (2002) ArticleTitleCerebral ischemia and trauma-different etiologies yet similar mechanisms: neuroprotective opportunities. Brain Res Brain Res Rev 39 55–73 Occurrence Handle12086708 Occurrence Handle10.1016/S0165-0173(02)00157-1

    Article  PubMed  Google Scholar 

  • SA Lipton PA Rosenberg (1994) ArticleTitleExcitatory amino acids as a final common pathway for neurologic disorders. N Engl J Med 330 613–622 Occurrence Handle7905600 Occurrence Handle10.1056/NEJM199403033300907 Occurrence Handle1:CAS:528:DyaK2cXltVGhtbk%3D

    Article  PubMed  CAS  Google Scholar 

  • S Love (2003) ArticleTitleApoptosis and brain ischaemia. Prog Neuropsychopharmacol Biol Psychiatry 27 267–282 Occurrence Handle12657366 Occurrence Handle10.1016/S0278-5846(03)00022-8 Occurrence Handle1:CAS:528:DC%2BD3sXit12ntrg%3D

    Article  PubMed  CAS  Google Scholar 

  • B Meldrum (1990) ArticleTitleProtection against ischaemic neuronal damage by drugs acting on excitatory neurotransmission. Cerebrovasc Brain Metab Rev 2 27–57 Occurrence Handle2169834 Occurrence Handle1:STN:280:By6D3c7lsFM%3D

    PubMed  CAS  Google Scholar 

  • JC Mills NL Stone RN Pittman (1999) ArticleTitleExtranuclear apoptosis. The role of the cytoplasm in the execution phase. J Cell Biol 146 703–708 Occurrence Handle10459006 Occurrence Handle10.1083/jcb.146.4.703 Occurrence Handle1:CAS:528:DyaK1MXls1Srtrc%3D

    Article  PubMed  CAS  Google Scholar 

  • JW Olney (1993) ArticleTitleRole of excitotoxins in developmental neuropathology. APMIS 40 IssueID[Suppl] 103–112 Occurrence Handle1:CAS:528:DyaK2cXktValt70%3D

    CAS  Google Scholar 

  • MR Pulera LM Adams H Liu DG Santos RN Nishimura F Yang GM Cole CG Wasterlain (1998) ArticleTitleApoptosis in a neonatal rat model of cerebral hypoxia-ischemia. Stroke 29 2622–2630 Occurrence Handle9836776 Occurrence Handle1:STN:280:DyaK1M%2FlsFKnsw%3D%3D

    PubMed  CAS  Google Scholar 

  • Rodriguez DM, Alonso TJ, Perdomo DJ, Gonzalez HT, Castro FR, Sabate M, Garcia DJ (2004) Glial regulation of nonsynaptic extracellular glutamate in the substantia nigra. Glia (in press)

  • A Saraste K Pulkki (2000) ArticleTitleMorphologic and biochemical hallmarks of apoptosis. Cardiovasc Res 45 528–537 Occurrence Handle10728374 Occurrence Handle10.1016/S0008-6363(99)00384-3 Occurrence Handle1:CAS:528:DC%2BD3cXltVGlsg%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • M Schwab I Antonow-Schlorke U Zwiener R Bauer (1998) ArticleTitleBrain-derived peptides reduce the size of cerebral infarction and loss of MAP2 immunoreactivity after focal ischemia in rats. J Neural Transm 53 IssueID[Suppl] 299–311 Occurrence Handle1:CAS:528:DyaK1cXmvVWnt7c%3D

    CAS  Google Scholar 

  • L Stoppini P Buchs D Muller (1993) ArticleTitleLesion-induced neurite sprouting and synapse formation in hippocampal organotypic cultures. Neuroscience 57 985–994 Occurrence Handle8309556 Occurrence Handle10.1016/0306-4522(93)90043-F Occurrence Handle1:STN:280:ByuC2c3ovV0%3D

    Article  PubMed  CAS  Google Scholar 

  • L Stoppini PA Buchs D Muller (1991) ArticleTitleA simple method for organotypic cultures of nervous tissue. J Neurosci Methods 37 173–182 Occurrence Handle1715499 Occurrence Handle10.1016/0165-0270(91)90128-M Occurrence Handle1:STN:280:By6A2M%2FosFI%3D

    Article  PubMed  CAS  Google Scholar 

  • Y Tatebayashi MH Lee L Li K Iqbal I Grundke-Iqbal (2003) ArticleTitleThe dentate gyrus neurogenesis: a therapeutic target for Alzheimer‘s disease. Acta Neuropathol (Berl) 105 225–232 Occurrence Handle1:CAS:528:DC%2BD3sXntV2iuw%3D%3D

    CAS  Google Scholar 

  • M Windisch A Gschanes B Hutter-Paier (1998) ArticleTitleNeurotrophic activities and therapeutic experience with a brain derived peptide preparation. J Neural Transm 53 IssueID[Suppl] 289–298 Occurrence Handle1:CAS:528:DyaK1cXmvVWnt7Y%3D

    CAS  Google Scholar 

  • R Wronski N Golob E Grygar M Windisch (2002) ArticleTitleTwo-color, fluorescence-based microplate assay for apoptosis detection. Biotechniques 32 666–668 Occurrence Handle11911668 Occurrence Handle1:CAS:528:DC%2BD38XitFCntr0%3D

    PubMed  CAS  Google Scholar 

  • R Wronski P Tompa B Hutter-Paier K Crailsheim P Friedrich M Windisch (2000) ArticleTitleInhibitory effect of a brain derived peptide preparation on the Ca++-dependent protease, calpain. J Neural Transm 107 145–157 Occurrence Handle10847556 Occurrence Handle10.1007/s007020050013 Occurrence Handle1:CAS:528:DC%2BD3cXisFeqtL8%3D

    Article  PubMed  CAS  Google Scholar 

  • AH Wyllie JF Kerr AR Currie (1980) ArticleTitleCell death: the significance of apoptosis. Int Rev Cytol 68 251–306 Occurrence Handle7014501 Occurrence Handle1:STN:280:Bi6C1M7jsFA%3D Occurrence Handle10.1016/S0074-7696(08)62312-8

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. JSW-Research, Institute of Experimental Pharmacology, Graz, Austria

    C. Riley, B. Hutter-Paier, M. Windisch & R. Wronski

  2. EBEWE Pharma, Unterach, Austria

    E. Doppler & H. Moessler

Authors
  1. C. Riley
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. B. Hutter-Paier
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M. Windisch
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. E. Doppler
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. H. Moessler
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. R. Wronski
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Riley, C., Hutter-Paier, B., Windisch, M. et al. A peptide preparation protects cells in organotypic brain slices against cell death after glutamate intoxication. J Neural Transm 113, 103–110 (2006). https://doi.org/10.1007/s00702-005-0302-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00702-005-0302-8

Search

Navigation